In vivo Imaging of the Therapeutic Efficacy and Fate of Bimodal Engineered Stem Cells in Malignant Brain Tumors.
In this study, we have developed an efficient stem cell based therapeutic strategy that simultaneously allows killing of tumor cells and assessment and eradication of SC post highly malignant glioblastoma multiforme (GBM) brain tumor treatment. Mesenchymal stem cells (MSC) engineered to co-express the prodrug converting enzyme, herpes simplex virus thymidine kinase (HSV-TK) and a potent and secretable variant of tumor necrosis factor apoptosis-inducing ligand (S-TRAIL) induced caspase mediated GBM cell death and showed selective MSC sensitization to the prodrug ganciclovir (GCV). A significant decrease in tumor growth and a subsequent increase in survival were observed when mice bearing a highly aggressive GBM were treated with MSC co-expressing S-TRAIL and HSV-TK. Furthermore, the systemi...